8-85342850-C-G

Position:

• chr8-85342850-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523022.6(CA1):​c.-24-1191G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,882 control chromosomes in the GnomAD database, including 21,792 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (21786 hom., cov: 31)
  • Exomes 𝑓: 0.78 (6 hom.)
• Consequence: CA1 ENST00000523022.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812

Genes affected

CA1 (HGNC:1368): (carbonic anhydrase 1) Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. This CA1 gene is closely linked to the CA2 and CA3 genes on chromosome 8. It encodes a cytosolic protein that is found at the highest level in erythrocytes. Allelic variants of this gene have been described in some populations. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CA1	NM_001128831.4	c.-24-1191G>C		intron_variant		ENST00000523022.6	NP_001122303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA1	ENST00000523022.6	c.-24-1191G>C		intron_variant		1	NM_001128831.4	ENSP00000429798	P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80321 AN: 151746 Hom.: 21776 Cov.: 31

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.560

GnomAD4 exome AF: 0.778 AC: 14 AN: 18 Hom.: 6 Cov.: 0 AF XY: 0.625 AC XY: 5 AN XY: 8

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.529 AC: 80359 AN: 151864 Hom.: 21786 Cov.: 31 AF XY: 0.530 AC XY: 39308 AN XY: 74202

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.558

Alfa AF: 0.429 Hom.: 1218

Bravo AF: 0.518

Asia WGS AF: 0.354 AC: 1231 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.66
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1032551; hg19: chr8-86255079; COSMIC: COSV56279901; COSMIC: COSV56279901;